B-Cell Depletion with Rituximab in Relapsing–Remitting Multiple Sclerosis

ABSTRACT

 Background  

There is increasing evidence that B lymphocytes are involved in the pathogenesis of multiple sclerosis, and they may be a therapeutic target.  Rituximab, a monoclonal antibody, selectively targets and depletes CD20+ B lymphocytes.   Methods  In a phase II, double-blind, 48-week trial involving 104 patients with relapsing–remitting multiple sclerosis, we assigned  

­	69	patients to receive 1000 mg of intravenous rituximab and
­	35	patients to receive placebo
­		on days 1 and 15.

 The primary end point was the total count of gadolinium-enhancing lesions detected on magnetic resonance imaging scans of the brain at weeks 12, 16, 20, and 24.  Clinical outcomes included safety, the proportion of patients who had relapses, and the annualized rate of relapse.   

Results  

As compared with patients who received placebo, patients who received rituximab had reduced counts of total gadolinium-enhancing lesions at weeks 12, 16, 20, and 24 (P<0.001) and of total new gadolinium-enhancing lesions over the same period (P<0.001); these results were sustained for 48 weeks (P<0.001).  As compared with patients in the placebo group, the proportion of patients in the rituximab group with relapses was significantly reduced at week 24 (14.5% vs.  34.3%, P=0.02) and week 48 (20.3% vs.  40.0%, P=0.04).   More patients in the rituximab group than in the placebo group had adverse events within 24 hours after the first infusion, most of which were mild-to-moderate events; after the second infusion, the numbers of events were similar in the two groups.   

Conclusions  

A single course of rituximab reduced inflammatory brain lesions and clinical relapses for 48 weeks.  This trial was not designed to assess long-term safety or to detect uncommon adverse events.  The data provide evidence of B-cell involvement in the pathophysiology of relapsing–remitting multiple sclerosis. 

Source Information

From the Department of Neurology,

University of California at San Francisco,

San Francisco (S.L.H., E.W.);

Montreal Neurological Institute,

McGill University (D.L.A., J.A., A.B.-O.), and

NeuroRx Research (D.L.A.) —

both in Montreal;

Barrow Neurology Clinics,

Phoenix, AZ (T.V.);

Mellen Center for Multiple Sclerosis,

Cleveland Clinic, Cleveland (R.J.F.);

Biogen Idec,

Cambridge, MA (M.P.); and

Genentech, South San Francisco, CA (N.S., S.A., A.L.-G., C.H.S.).